Using molecular dynamics simulation to explore the binding of the potent anticancer drugs sorafenib and streptozotocin, to functionalized carbon nanotubes
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Asma Soofi,1,*
1. University of Tehran Department of Physical Chemistry
- Introduction: Chemotherapy is a standard cancer treatment and scientists have proposed a variety of anticancer drugs for use in cancer treatment, but poor water solubility and serious adverse effects have limited the efficacies of many of those potent and promising drug molecules. These complications might be reduced by the use of a nanocarrier that targets the tumor site and only releases the drug at that site. Carbon nanotubes (CNTs) are among the most promising candidates for use as drug-delivery carriers. Carbon nanotubes (CNTs) are widely used in drug delivery systems (DDSs) due to their unique chemical and physical properties. Investigation of interactions between biomolecules and CNTs is an interesting and important subject in biological applications. In this study, Molecular Dynamics (MD) simulation is used to study the behavior of the anticancer drugs sorafenib (SF) and streptozotocin (STZ) on free and functionalized carbon nanotubes (FCNTs). The carbon nanotube has functionalized with valine or phenylalanine moieties to reduce their toxicity and increase their solubility in aqueous solutions
- Methods: A series of MD simulations were carried out on different models to explore the interactions of anticancer drugs (SF, STZ) with carbon nanotubes. In all of the simulation model systems, an armchair single-walled carbon nanotube with a length of ∼ 42 Å and a diameter of ∼ 21 Å was used as the nanocarrier. The CNT model was generated using the TubeGen online server. In each FCNT, four functional groups were placed on the sidewalls of the nanotube. The GROMACS software package (version 4.5.4) with the CHARMM27 force field was used to perform all of the molecular dynamics simulations carried out in this work. A box of dimensions 6 × 6 × 6 nm was chosen for each of the systems, and the TIP3P water model was employed to fill the simulation box. The particle mesh Ewald (PME) method was used to describe long-range electrostatic interaction. The pressure (1 bar) and the temperature (310 K) were kept stable using the Berendsen algorithm and the Visual Molecular Dynamics (VMD) software was used to visualize the studied system.
- Results: The influences of the positions and type of the functional groups present on the adsorption behavior of the anticancer drugs were investigated using molecular dynamics simulations. To verify the stability of the studied systems, the total energy, and the number of hydrogen were plotted.
We can see that in each case the vdW energy dropped drastically and then fluctuated slightly until the end of the simulation. Thus, the vdW energy plays a significant role in the stability of the studied systems and the initial adsorption of the drugs. It is worth pointing out that the anticancer drug STZ has the lowest van der Waals energy with the CNT, with a value of ~ −248.87 kJ/mol. Note that pristine CNT is not capable of forming hydrogen bonds, so no hydrogen bonds were observed between the drug molecules and the carbon atoms of a pristine nanotube. Analysis of the hydrogen bonds revealed that the numbers of drug–functional group and drug–water hydrogen bonds were greater for STZ than for SF. This behavior can be explained by the presence of several hydroxyl groups in the structure of STZ
- Conclusion: The MD simulations revealed that functionalizing the CNT can affect the strength of the drug–carrier interaction. It was found that the average van der Waals interaction energies between the drugs and FCNTs functionalized with valine were more negative than the corresponding energies when the FCNTs were functionalized with phenylalanine indicating that the van der Waals interaction energy between an anticancer drug and a FCNT can be affected by the positions of the functional groups on the CNT. Moreover, the drugs interacted more strongly with valine groups than with phenylalanine groups.
- Keywords: anticancer drugs
Molecular Dynamics (MD) simulation
Carbon nanotubes
